1. Field of the Invention
The present invention relates generally to a method for film coating the surface of porous micro beads having pores containing active components with silicone or its derivatives, and cosmetic and pharmaceutical compositions for dermal application containing porous micro beads silicone-coated by the film coating method.
2. Description of the Related Art
Ingredients such as vitamins, antioxidants and enzymes are known to have effects of, for example, whitening, wrinkle clearing, increasing skin""s elasticity, noxious oxygen removing, etc. and have been widely used as active components of cosmetic and pharmaceutical compositions for dermal application. However, when exposed to light or air, the active components are susceptible to oxidation and destruction and thus limited in their applications. Oxidation of the active components causes not only a deterioration of potency but also discoloration, for example, browning or yellowing depending on the type of the active components.
Such an oxidative destruction accelerates for active components that are present in an aqueous phase or in contact with water.
In connection to this, there have been suggested a number of methods for stabilization of the active components by minimizing contact of the active components with water.
A method for formulating active components into dry powder (see. Japanese Patent Application Laid-open So 63-130514) is effective in maintaining stability of the active components to a certain extent but confined in formulation to powder. Thus the method is inapplicable to general cosmetic compositions of which the typical formulation is emulsion.
In an alternative method to cope with the problem, two separate containers are packed with powdery active components and an emulsified cosmetic liquid, respectively, for the user to mix prior to application (see. U.S. Pat. No. 4,818,512). However, this method is problematic in regard to inconvenience for the user who has to mix the contents of the two containers before use, and high expense of the packages.
An anhydrous formulation containing no moisture (see. U.S. Pat. No. 5,322,683) may retain stability of active components but is confined to powder. Also, the anhydrous formulation gives an unpleasant feeling to the skin because of its greasy property and is especially inapplicable to water soluble active components.
There have been proposed further another methods involving addition of polyhydric alcohols such as glycerin, or other organic solvents compatible with water (see. U.S. Pat. Nos. 5,703,041 and 4,983,382; JP Patent No. 44-22312; and U.S. Pat. No. 4,372,874). These methods stabilize the active components to a certain extent but give an unpleasant feeling to the skin due to its stickiness peculiar to polyhydric alcohols. Especially, organic solvents useful for stabilization of the active components, such as dimethylsulfoxide are normally toxic to the human body.
Besides, a method has been reported to utilize microcapsules and stabilize active components with a physical layer formed on the outer surface of the active components (Simon Benita (ed), 1996, Microencapsulation: Methods and industrial applications, Marcel Dekker, Inc. New York). The microcapsules are however unsatisfactory to achieve complete stabilization of the active components, because the coating on the wall material constituting the microcapsules permits entrance of water and allows active components to dissolve out through diffusion.
An alternative method involves retaining active components in the pores of porous microbeads in the same manner as the previously stated microcapsules (William Klein and Alfred DiSapio, 1989, HAPPI magazine, 26:7; U.S. Pat. No. 5,145,675). In contrast to the microcapsules where the capsule constituents provide a complete physical separation of the internal phase of the capsules from the external one, the porous microbeads have the internal phase in communication with the external one through pores containing active components.
One aspect of the present invention provides a composition for use in dermal application. The composition comprises a plurality of particles having an internal structure of pores, a chemical compound contained in the internal structure of the porous particles, and a layer of coating over each of the particles, containing at least one of a silicone and a polysiloxane-based compound.
Another aspect of the present invention provides a method of making a composition. The method comprises the steps of: preparing a plurality of particles containing a chemical compound in an internal structure thereof; preparing a coating mixture comprising at least one of a silicone and a polysiloxane-based compound with a solvent; mixing the plurality of particles with the coating mixture, whereby the coating mixture covering over the particles; and evaporating the solvent from the coating mixture covering over the particles.
In the microbead system retaining active ingredients within the pores, the stability and efflux of the active ingredients significantly depend upon their physiochemical properties and the ambient solvent constituting the internal phase as well as those of the outer base constituting the external phase due to communication between internal and external phases. For example, if the active components adsorbed in the pores or the solvent dissolving the active components within the pores have high affinity to the base of the external phase, the active components are susceptible to effusion and their stability deteriorates significantly. Thus, the internal phase of the pores must not have affinity to the base of the external phase in a composition containing active components.
Especially, in order to stabilize active components susceptive to water, the active components must have minimized contact with water while they are contained in the pores. However, a general cosmetic composition has the formulation of emulsion containing a large amount of surfactant such that two solvents naturally immiscible with each other, such as water and oil, are mixed together in no small amount. Thus, the stability of the active components in a cosmetic composition actually depends upon the physiochemical properties of the active components and the external base.
According to one aspect of the present invention, active ingredients of a cosmetic or pharmaceutical composition are retained in the internal structure of porous particles or microbeads. Thereafter, the particles or microbeads containing the active ingredients are coated with a thin film of a material.
First, active ingredients of a cosmetic or pharmaceutical composition are dissolved in a solvent selected from the group consisting of methanol, ethanol, glycerin alone, and mixtures thereof. The resulting solution or suspension is subject to physical contact with porous particles or microbeads to retain the active components in their internal structure of pores. The porous microbeads retaining the active components are separated from the solution or suspension by filtration. The residual solvent of the microbeads is removed and the active components impregnated within the internal structure of the microbeads by subsequent vacuum drying and washing processes.
The porous particles or microbeads have an internal structure of interconnected matrix structure, in which the active components are retained or impregnated. The active ingredients effuse from internal structure by capillary action when the porous particles or microbeads are applied to skin or other surfaces.
The porous microbeads usable in the present invention are prepared through formation of pores with three-dimensional cross-links of a polymer or copolymer. Examples of the polymer or copolymer include, but are not limited to polymethacrylic acid copolymer, polymethylmethacrylic acid copolymer, allyl-polymethacrylic acid copolymer, polystyrene polymer, polyethylcellulose polymer, and silicagel. All the polymers or copolymers are commercially available as well as porous microbeads formed from the three-dimensional cross-links thereof and, of course, may be chemically synthesized by those skilled in the art.
Preferably, the porous microbeads are about 1xcx9c500 xcexcm in diameter and 5xcx9c50 xcexcm in diameter distribution.
Higher porosity of the particles or microbeads would be better to retain a higher amount of the active components, but may incur relative deterioration of the mechanical strength of the porous microbeads, which is problematic in preparation of the composition containing the porous microbeads. It is thus preferable that the porous microbeads are chosen in accordance with the characteristics based on the workability of the formulation and the degree of retainment of the active components.
As the pores of the porous microbeads formed through three-dimensional cross-links of the polymer are typically less than 0.5 xcexcm in size, the active components are difficult to adsorb in the pores if they are not in the solution state. The solvent for dissolving the active components has to meet the following requirements: (1) well dissolving a large amount of active components; (2) not inhibiting retainment of the active components in the pores; and (3) if toxic to human body or irritative to the skin, easiness of removal after retaining the active components in the particles or microbeads.
Examples of the solvent suitable for use in retaining the active components in the pores of the porous microbeads include methanol and ethanol, which are capable of dissolving almost water-soluble and fat-soluble active components of high content and easily removable by a known method such as drying.
As the solvent, glycerin may reduce retaining rate of the active components due to its high viscosity but exhibits high solubility for water-soluble active components such as L-ascorbic acid, without incurring stimuli to the skin.
Retaining the active components in the pores of the porous microbeads is typically achieved through a physical contact of the porous microbeads with a solution of the active components. Any methods for facilitating the retainment of the active components in the pores can be used, such as stirring or heating the dispersed solution of the porous microbeads or addition of a surfactant. A known method to retain chemicals in porous microbeads is disclosed in HAPPI magazine, 1989, 26:7 by William Klein and Alfred DiSapio and in U.S. Pat. No. 5,145,675, which are hereby incorporated herein by reference. According to the disclosure, the adsorption rate of the active components per unit weight of the porous microbeads varies depending on the properties of the active components and the type of the solvent. For L-ascorbic acid, for example, the adsorption rate is about 20xcx9c90 wt. % when using one of the above-mentioned solvents alone, or mixtures thereof.
After retaining the active components in the pores, the porous microbeads are separated through a filtration and then washed in order to remove a residual solution of the active components on the surface of the porous microbeads and among the granules of them. An excess of the solution remaining on the surface of the porous microbeads and among the granules of them may not only inhibit the film coating process of the present invention later described, but also deteriorate stability of the active components through effusion, in case of cosmetic and pharmaceutical compositions.
The washing solvent as used herein has to meet the following requirements: low solubility to the active components and high compatibility with the solvent of the solution containing the active components. A suitable washing solvent is isopropanol or acetone for L-ascorbic acid.
The washing process includes adding the washing solvent to the filter cake of the porous microbeads obtained by filtration, and performing a second filtration. Alternatively, the washing process includes, if necessary, separate removal of the filter case, dispersing the separated filter cake in the washing solvent for washing, and then performing a second filtration. The former method is usually preferred because excessive washing of the filter cake may lead to a loss of the active components retained by the pores.
For removal of the residual solvent in the pores after the washing process, the porous microbeads are dried under atmospheric pressure or vacuum. The drying process typically completes within one day under vacuum but the drying period may be varied depending on the volatility of the solvent. For methanol as the solvent, the drying period is usually one day under vacuum.
After the completion of washing and drying, the porous microbeads have the form of powdery solid. The active components remain in the solid state within the pores if the solvent is completely removed through the drying process, or in the state of supersaturated solution if part of the solvent resides in the pores.
At this stage, addition of the porous microbeads to an emulsified or dispersed cosmetic composition results in significant deterioration of the stability of the active components that are compatible with the external base, since the active components adsorbed by the porous microbeads are ready to effuse. For example, in a case where porous microbeads containing L-ascorbic acid (vitamin C) very soluble in water is added to a normal water-in-oil type emulsion, L-ascorbic acid becomes in contact with water as the external phase and easily effuses, thereby resulting in abrupt deterioration of the stability.
To prevent such a deterioration of the stability of the active components, the present invention film coats the surface of the porous microbeads adsorbing the active components with an appropriate compound for preventing water penetration into the surface of the porous microbeads.
The film coating for this purpose has not to permanently inhibit communication between the exterior and interior of the pores of the porous microbeads.
A permanent film coating of the pores to block the communication between the exterior and interior of the pores may increase stability of the active components but cannot realize efficacy of the active components in a cosmetic or pharmaceutical composition because the active components cannot effuse from the pores when applied to the skin.
The inventor of this invention selects silicone and its derivatives as a film coating agent. Silicone and its derivatives present some advantages including: (1) water repellency sufficient to prevent penetration of water into the pores; (2) immiscibility with almost cosmetic oils; (3) commercial availability; (4) strong binding force with the porous microbeads by way of reactive functional groups for effective film coating; and (5) innoxiousness to the human body.
Hereafter, a description will be made in detail as to a film coating method for the above-prepared porous microbeads containing active components with silicone or its derivatives. There are two methods for film coating the porous microbeads with silicone or its derivatives.
The one method involves using a mixture of silicone as a film coating agent and an organic solvent of high melting capacity for silicone, high volatility and low melting capacity for active components.
Examples of the silicone suitable for the above purpose include methicone, dimethicone, dimethicone copolyol and its derivatives, dimethiconol and its derivatives, and a variety of copolymers, with dimethicone being most preferred.
Examples of the volatile organic solvent include dichloromethane, chloroform, ethyl acetate, and acetone, with dichloromethane being most preferred.
The silicone is preferably added in a range of about 5xcx9c50 wt. %, based upon the total weight of the porous microbeads for film coating. With the silicone content less than 5 wt. %, the obtained porous microbeads are incompletely film coated. In contrast thereto, the film coating is excessively thickened or silicone oil aggregates not adsorbed by the surface of the porous microbeads occur with the silicone content greater than 50 wt. %.
The volatile solvent is added in such an appropriate amount as to maintain fluidity after dispersion of the porous microbeads.
The porous microbeads containing the water soluble active components are dispersed in a mixed solution of the silicone and the volatile solvent, and thereafter, the resulting mixture is subjected to drying or vaporization under atmospheric pressure or vacuum while stirring. Thus the volatile solvent is removed and the silicone aggregates on the surface of the porous microbeads to form a silicone film.
Upon vaporization of almost the volatile solvent, film coated porous microbeads are obtained in the form of powder. Then, drying is performed under vacuum in order to completely remove the volatile solvent.
The other method for film coating the porous microbeads with silicone or its derivatives involves using a mixture of a polysiloxane-based compound as a film coating agent, with optionally a silane-based compound.
The polysiloxane-based compound suitable for use in this method is usually polydimethylsiloxane-based derivatives and has reactive functional groups at both terminals or an intermediate portion of the straight chain. Hardening occurs due to cross-linking of the polysiloxane-based compound alone or together with the silane-based compound. The reactive functional groups are hydroxyl (xe2x80x94OH), chloride (xe2x80x94Cl), and hydrogen (xe2x80x94H) and directly bonded to silicone (Si) of polysiloxane. For the reactive functional group, the hydroxyl group or chloride is usually located at both terminals of the polymethylsiloxane chain, and the hydrogen is located at the intermediate portion as well as both terminals of the chain, in which case the compound is called poly(dimethylsiloxane-co-methylhydrosiloxane). Methylhydrosiloxane monomers containing hydrogens are preferably present in an amount of less than 20% based on the total weight of the copolymer. This is because, in a case of incomplete reaction, the higher hydrogen content sometimes causes the film coated porous microbeads to react with water contained in the final product such as cosmetic compositions and generate hydrogen gas.
The silane-based compound is an alkoxysilane compound containing three or four ethoxyl groups and, the examples thereof include tetramethoxy silane, tetraethoxysilane, methyltrimethoxysilane, xe2x80x94methacryloxypropyltrimethoxysilane, xe2x80x94and glycydoxypropyltrimethoxysilane.
The reaction mechanism can be expressed by the reaction formula 1: 
In the reaction formula 1, R of the reactant 2 is methyl or ethyl when X of the reactant 1 is hydroxyl (xe2x80x94OH), or solely H when X of the reactant 1 is H or Cl; the reactant 1 represents a reactive polysiloxane-based compound; and the reactant 2 represents a silane-based compound wherein R of the reactant 2 is methyl or ethyl, or a polysiloxane-based compound wherein R of the reactant 2 is H.
The silane-based compound reacts with three or four polysiloxane molecules in the above mechanism and serves as a cross-link agent. The silane-based compound has to be added during formation of the film coating when the porous microbeads are free from a reactive functional group such as a hydroxyl group on. The porous microbeads having hydroxyl groups, such as silicagel may participate in direct reaction with the reactive functional groups of the polysiloxane, in which case the film coating can also be formed with a reactive polysiloxane-based compound alone or mixtures thereof.
A solvent for dissolving the polysiloxane-based compound and the silane-based compound is selected depending upon the desired types of polysiloxane-based compound and the silane-based compound and the active compounds adsorbed by the porous microbeads. Typically, the suitable solvent is an organic solvent for water-soluble active components, and used in the form of a water-in-oil type emulsion for fat-soluble active components.
A detailed description will be given below to a film coating method using a mixture of a polysiloxane-based compound and optionally a silane-based compound.
A silicone mixture of a reactive polysiloxane-based compound alone or a mixture of at least two reactive polysiloxane-based compounds, and optionally a silane-based compound is dissolved in an organic solvent such as dichloromethane or chloroform, or in the form of a water-in-oil type emulsion. The silane-based compound is preferably present in an amount of less than 10% of the reactive polysiloxane-based compound. An excess of the silane-based compound decreases polymerization degree with excessively increased consistency of the film and remains substances that have not been participated in the reaction, thereby adversely affecting the skin. If necessary, a catalyst such as zinc octoate and dibutyltin dilaurate is added in an amount of about 0.1xcx9c4 wt. % based on the total weight of the polysiloxane-based compound. Thereafter, porous microbeads retaining active components are added and stirred for 2xcx9c3 hours for uniform mixing. The added amount of the reactive polysiloxane-based compound is in the range of about 1xcx9c100 wt. % based on the total weight of the porous microbeads since the porosity depends on the type of the porous microbeads. The mixture is heated in a reactor with a condenser under stirring, while maintaining at 40xc2x0 C. to evaporate the solvent. The resulting porous microbeads are maintained at the room temperature for about three days to remove the residual solvent. The porous microbeads are in some cases washed with a solvent such as isopropanol in order to remove substances that have not been participated in the reaction.
The second film coating method maintains a predetermined distance between the film and the surface of the porous microbeads and therefore promotes water repellency of the porous microbeads. Thus the film coating process is practicable prior to adsorption of the active components so that the biological active components such as enzymes can be stabilized during in contact with an organic solvent or oils.